An underlying principle that governs drug-metabolizing enzymes is their broad structural diversity with a loose link to specificity. Numerous regulatory proteins dictate induction of the enzymes. Some of these proteins also exhibit structural diversity and functional promiscuity, which may also be a reflection of protein modifications and protein-protein interactions. Our basic research aims are to understand the underlying structural basis governing the functions of metabolic enzymes and the proteins that regulate expression of the enzymes. We have chosen to investigate molecular and cellular mechanisms of phenobarbital (PB) induction. PB represents a group of myriad xenobiotics that induce drug-metabolizing enzymes.A signature of PB induction is its pleiotropicity altering the expression of a large number of hepatic genes.Some of those alterations are coordinated to achieve a physiological and/or pharmacological end-point. PB also acts as tumor promoter, causing hepatocellular carcinomas in rodents.